Implant- and anesthesia-related factors affecting cardiopulmonary threshold intensities for vagus nerve stimulation

Abstract Objective. Vagus nerve stimulation (VNS) is typically delivered at increasing stimulus intensity until a neurological or physiological response observed (‘threshold’) for dose calibration, preclinically and therapeutically. Factors affecting VNS thresholds have not been studied systematically. In rodent model of we measured neural responses to intensity, determined examined the effect implant- anesthesia-related factors on thresholds. Approach. acute chronic vagus implants (45 20 rats, respectively) was under isoflurane, ketamine-xylazine, awake conditions. Evoked compound action potentials (CAPs) were recorded activation different fiber types extracted. Elicited registered, including changes in heart rate (HR), breathing (BR), blood pressure (BP). CAP determined. Main results . The threshold evoking discernable CAPs (>10 µ V) (CAP threshold) significantly lower than what elicits 5%–10% drop (heart threshold, HRT) (25 A ± 1.8 vs. 80 5.1, respectively; mean SEM). Changes BP small BR (bradypnea) occur lowest intensities (70 8.3), followed by HR (80 5.1) finally significant (apnea) (310 μ 32.5). HRT electrode impedance are correlated (Pearson correlation r = 0.47; p < 0.001) but ( −0.34; NS); both increase with implant age 0.44; 0.001 0.64; 0.001, respectively). when animals (200 35.5), ketamine-xylazine (640 151.5), isoflurane (1000 139.5). sequence same anesthetized animals. Pulsing frequency affects CAPs. Significance Implant age, impedance, type anesthesia affect should be accounted calibrating dose.